Abstract:

Dynamic sensor calibration schedule management including determining a
stability profile of an in vivo analyte sensor in fluid contact with a
biological fluid, processing the determined stability profile in
conjunction with calibration criteria for the analyte sensor, and
modifying a predetermined sensor calibration schedule based on the
processed stability profile is provided.

Claims:

1. A method, comprising:determining a stability profile of an in vivo
analyte sensor in fluid contact with a biological fluid, determining the
stability profile including:detecting the onset of a calibration routine
initialization within a predetermined time period;performing stability
analysis of the analyte sensor; andtime shifting the calibration routine
initialization to start at a time period different from the predetermined
time period;processing the determined stability profile in conjunction
with calibration criteria for the analyte sensor; andmodifying a
predetermined sensor calibration schedule based on the processed
stability profile.

2. The method of claim 1, wherein time shifting includes executing the
calibration routine following the stability analysis of the analyte
sensor.

3. The method of claim 1, wherein time shifting includes delaying the
calibration routine initialization past the predetermined time period.

4. The method of claim 1, wherein the analyte sensor includes a glucose
sensor.

5. The method of claim 1, wherein the determined stability profile
includes a predetermined time period during which the analyte sensor is
stable.

7. The method of claim 1, wherein time shifting the calibration routine
initialization includes delaying a subsequent scheduled calibration
event.

8. A method, comprising:initializing an analyte sensor;activating a timer
associated with the analyte sensor, the timer related to a stability
profile of the analyte sensor;calibrating the analyte sensor based on a
time corresponding reference data based at least in part on a
predetermined calibration schedule including a plurality of time periods
for performing calibration over the life of the sensor; andmodifying the
calibration schedule to time shift the plurality of time periods for
performing calibration.

10. The method of claim 8, wherein the stability profile includes a
predetermined time period associated with the sensor stability.

11. The method of claim 8, wherein the reference data is associated with a
time corresponding sensor data.

12. The method of claim 8, wherein the reference data is obtained from an
in vitro blood glucose meter.

13. A method, comprising:detecting an input value associated with a
reference data;verifying that an analyte sensor is within its calibration
stability duration;calibrating the analyte sensor based on the detected
input value; andtime shifting the initiation of the one or more
subsequent scheduled calibration events for the analyte sensor.

14. The method of claim 13, wherein the reference data is received from a
blood glucose monitor.

15. The method of claim 13, wherein calibrating the analyte sensor
includes determining a sensitivity value associated with the sensor.

16. The method of claim 15, wherein the sensitivity is determined based at
least in part on the detected input value associated with the reference
data.

18. The method of claim 17, wherein the sensor manufacturing information
includes a date of manufacture of the analyte sensor.

19. An apparatus, comprising:one or more processors;a memory for storing
instructions which, when executed by the one or more processors, causes
the one or more processors to determine a stability profile of an in vivo
analyte sensor in fluid contact with a biological fluid by detecting the
onset of a calibration routine initialization within a predetermined time
period, performing stability analysis of the analyte sensor, and time
shifting the calibration routine initialization to start at a time period
different from the predetermined time period, to process the determined
stability profile in conjunction with calibration criteria for the
analyte sensor, and to modify a predetermined sensor calibration schedule
based on the processed stability profile.

20. The apparatus of claim 19, wherein the memory for storing instructions
which, when executed by the one or more processors, causes the one or
more processors to execute the calibration routine following the
stability analysis of the analyte sensor.

22. The apparatus of claim 19, wherein the memory for storing instructions
which, when executed by the one or more processors, causes the one or
more processors to delay the calibration routine initialization past the
predetermined time period.

23. The apparatus of claim 19, wherein the analyte sensor includes a
glucose sensor.

24. The apparatus of claim 19, wherein the determined stability profile
includes a predetermined time period during which the analyte sensor is
stable.

26. The apparatus of claim 19, wherein the memory for storing instructions
which, when executed by the one or more processors, causes the one or
more processors to delay subsequent scheduled calibration event.

27. An apparatus, comprising:one or more processors;a memory for storing
instructions which, when executed by the one or more processors, causes
the one or more processors to initialize an analyte sensor, activate a
timer associated with the analyte sensor, the timer related to a
stability profile of the analyte sensor, calibrate the analyte sensor
based on a time corresponding reference data based at least in part on a
predetermined calibration schedule including a plurality of time periods
for performing calibration over the life of the sensor, and modify the
calibration schedule to time shift the plurality of time periods for
performing calibration.

28. The apparatus of claim 27, wherein the memory for storing instructions
which, when executed by the one or more processors, causes the one or
more processors to determine sensor stability.

29. The apparatus of claim 27, wherein the stability profile includes a
predetermined time period associated with the sensor stability.

30. The apparatus of claim 27, wherein the reference data is associated
with a time corresponding sensor data.

31. The apparatus of claim 27, wherein the reference data is obtained from
an in vitro blood glucose monitor.

32. An apparatus, comprising:one or more processors;a memory for storing
instructions which, when executed by the one or more processors, causes
the one or more processors to detect an input value associated with a
reference data, verify that an analyte sensor is within its calibration
stability duration, calibrate the analyte sensor based on the detected
input value, and time shift the initiation of the one or more subsequent
scheduled calibration events for the analyte sensor.

33. The apparatus of claim 32, wherein the memory for storing instructions
which, when executed by the one or more processors, causes the one or
more processors to determine a sensitivity value associated with the
sensor.

34. The apparatus of claim 33, wherein the sensitivity is determined based
at least in part of on the detected input value associated with the
reference data.

36. The apparatus of claim 32, wherein the sensor manufacturing
information includes a date of manufacture of the analyte sensor.

Description:

RELATED APPLICATIONS

[0001]The present application claims priority under 35 U.S.C. §119(e)
to U.S. provisional application No. 61/173,593 filed Apr. 28, 2009,
entitled "Dynamic Analyte Sensor Calibration Based On Sensor Stability
Profile", the disclosure of which is incorporated in its entirety by
reference for all purposes.

BACKGROUND

[0002]There are a number of instances when it is desirable or necessary to
monitor the concentration of an analyte, such as glucose, lactate, or
oxygen, for example, in bodily fluid of a body. For example, it may be
desirable to monitor high or low levels of glucose in blood or other
bodily fluid that may be detrimental to a human. In a healthy human, the
concentration of glucose in the blood is maintained between about 0.8 and
about 1.2 mg/mL by a variety of hormones, such as insulin and glucagons,
for example. If the blood glucose level is raised above its normal level,
hyperglycemia develops and attendant symptoms may result. If the blood
glucose concentration falls below its normal level, hypoglycemia develops
and attendant symptoms, such as neurological and other symptoms, may
result. Both hyperglycemia and hypoglycemia may result in death if
untreated. Maintaining blood glucose at an appropriate concentration is
thus a desirable or necessary part of treating a person who is
physiologically unable to do so unaided, such as a person who is
afflicted with diabetes mellitus.

[0003]Certain compounds may be administered to increase or decrease the
concentration of blood glucose in a body. By way of example, insulin can
be administered to a person in a variety of ways, such as through
injection, for example, to decrease that person's blood glucose
concentration. Further by way of example, glucose may be administered to
a person in a variety of ways, such as directly, through injection or
administration of an intravenous solution, for example, or indirectly,
through ingestion of certain foods or drinks, for example, to increase
that person's blood glucose level.

[0004]Regardless of the type of adjustment used, it is typically desirable
or necessary to determine a person's blood glucose concentration before
making an appropriate adjustment. Typically, blood glucose concentration
is monitored by a person or sometimes by a physician using an in vitro
test that requires a blood sample. The person may obtain the blood sample
by withdrawing blood from a blood source in his or her body, such as a
vein, using a needle and syringe, for example, or by lancing a portion of
his or her skin, using a lancing device, for example, to make blood
available external to the skin, to obtain the necessary sample volume for
in vitro testing. The fresh blood sample is then applied to an in vitro
testing devices such as an analyte test strip, whereupon suitable
detection methods, such as calorimetric, electrochemical, or photometric
detection methods, for example, may be used to determine the person's
actual blood glucose level. The foregoing procedure provides a blood
glucose concentration for a particular or discrete point in time, and
thus, must be repeated periodically, in order to monitor blood glucose
over a longer period.

[0005]Conventionally, a "finger stick" is generally performed to extract
an adequate volume of blood from a finger for in vitro glucose testing
since the tissue of the fingertip is highly perfused with blood vessels.
These tests monitor glucose at discrete periods of time when an
individual affirmatively initiates a test at a given point in time, and
therefore may be characterized as "discrete" tests. Unfortunately, the
fingertip is also densely supplied with pain receptors, which can lead to
significant discomfort during the blood extraction process.
Unfortunately, the consistency with which the level of glucose is checked
varies widely among individuals. Many diabetics find the periodic testing
inconvenient and they sometimes forget to test their glucose level or do
not have time for a proper test. Further, as the fingertip is densely
supplied with pain receptors which causes significant discomfort during
the blood extraction process, some individuals will not be inclined to
test their glucose levels as frequently as they should. These situations
may result in hyperglycemic or hypoglycemic episodes.

[0006]In addition to the discrete or periodic, in vitro, blood glucose
monitoring systems described above, at least partially implantable, or in
vivo, glucose monitoring systems, which are designed to provide
continuous or semi-continuous in vivo measurement of an individual's
glucose concentration. A number of these in vivo systems are based on
"enzyme electrode" technology, whereby an enzymatic reaction involving an
enzyme such as glucose oxidase, glucose dehydrogenase, or the like, is
combined with an electrochemical sensor for the determination of an
individual's glucose level in a sample of the individual's biological
fluid. By way of example, the electrochemical sensor may be placed in
substantially continuous contact with a blood source, e.g., may be
inserted into a blood source, such as a vein or other blood vessel, for
example, such that the sensor is in continuous contact with blood and can
effectively monitor blood glucose levels. Further by way of example, the
electrochemical sensor may be placed in substantially continuous contact
with bodily fluid other than blood, such as dermal or subcutaneous fluid,
for example, for effective monitoring of glucose levels in such bodily
fluid, such as interstitial fluid.

[0007]Relative to discrete or periodic monitoring using analyte test
strips, subcutaneous continuous monitoring is generally more desirable in
that it may provide a more comprehensive assessment of glucose levels and
more useful information, including predictive trend information, for
example. Subcutaneous continuous glucose monitoring is also desirable as
it is typically less invasive than discrete or periodic glucose
monitoring in blood accessed from a blood vessel.

[0008]Regardless of the type of implantable analyte monitoring device
employed, it has been observed that transient, low sensor readings which
result in clinically significant sensor related errors may occur for a
period of time. For example, it has been found that during the initial
12-24 hours of sensor operation (after implantation), a glucose sensor's
sensitivity (defined as the ratio between the analyte sensor current
level and the blood glucose level) may be relatively low--a phenomenon
sometimes referred to as "early signal attenuation" (ESA). Additionally,
low sensor readings may be more likely to occur at certain predictable
times such as during night time use--commonly referred to as "night time
drop outs". An in vivo analyte sensor with lower than normal sensitivity
may report blood glucose values lower than the actual values, thus
potentially underestimating hyperglycemia, and triggering false
hypoglycemia alarms.

[0009]Spurious low readings or drop outs may be caused by the presence of
blood clots also known as "thrombi" that form as a result of insertion of
the sensor in vivo. Such clots exist in close proximity to a subcutaneous
glucose sensor and have a tendency to "consume" glucose at a high rate,
thereby lowering the local glucose concentration. It may also be that the
implanted sensor constricts adjacent blood vessels thereby restricting
glucose delivery to the sensor site.

[0010]While these transient, low readings are infrequent and, in many
instances, resolve after a period of time, the negative deviations in
sensor readings impose constraints upon analyte monitoring during the
period in which the deviations are observed. One manner of addressing
this problem is to configure the analyte monitoring system so as to delay
reporting readings to the user until after this period of negative
deviations passes. Another way of addressing negative deviations in
sensor sensitivity is to require frequent calibration of the sensor. This
is often accomplished in the context of continuous glucose monitoring
devices by using a reference value after the sensor has been positioned
in the body, where the reference value most often employed is obtained by
a finger stick and use of a blood glucose test strip.

[0011]Notwithstanding the environmental effects on the sensitivity of
subcutaneously implanted sensors in general, continuous analyte
monitoring sensors designed according to identical specifications and
fabricated by the same processes and equipment may have variations in
sensitivity, e.g., variations in sensitivity amongst sensors of the same
lot or batch and/or between sensors of different lots. The variations may
be due to inconsistency in the registration of the material layers, i.e.,
misalignment of the layer edges relative to each other. Additionally,
inconsistencies in the volume/area of the various materials as they are
being deposited or dispensed may occur. Still yet, inconsistencies in the
spatial resolution or edge definition of the various materials on the
substrate can cause variations in sensitivity.

[0012]Due to these registration, deposition and resolution
inconsistencies, in certain instances, some form of calibration may be
required prior to use of the sensor to measure analyte, and/or oftentimes
a user may also need to perform a number of calibrations during the time
period that the sensor is used. One way this "individual-specific
calibration" is accomplished is by calibrating a continuous analyte
sensor against a reference value after the sensor has been positioned in
the body of a user, where the reference value most often used by users of
continuous glucose monitoring devices is a blood glucose test strip.
Typically, glucose monitoring systems' calibration time periods may be
predetermined and based on a fixed schedule during sensor use. When
successful sensor calibration is not performed, the system may no longer
display or output real time or substantially real time monitored glucose
levels.

[0013]Such calibration schedule may increase the level of inconvenience to
the user or sub-optimal use of the monitoring system, where missed
calibration event during the sensor wear results in the system
temporality or permanently shutting down until sensor is calibrated. For
example, when the calibration schedule is fixed and is determined from
when the sensor is first positioned in contact with the user's analyte,
and the calibration time period falls when it is not convenient or
practical to the user, the convenience of the analyte monitoring system
may be diminished. That is, depending on when the sensor is first
inserted through the skin layer of the patient and initialized for
operation (e.g. analyte monitoring), the scheduled calibration time
period may fall at night time (for example, when the user is sleeping),
or during the day, but when the user is not able to perform the in vitro
blood glucose testing to calibrate the sensor (for example, when in
meetings, engaged in physical or other activities, and the like).

SUMMARY

[0014]1. Embodiments include a method comprising determining a stability
profile of an in vivo analyte sensor in fluid contact with a biological
fluid, determining the stability profile including, detecting the onset
of a calibration routine initialization within a predetermined time
period, performing stability analysis of the analyte sensor, and time
shifting the calibration routine initialization to start at a time period
different from the predetermined time period, processing the determined
stability profile in conjunction with calibration criteria for the
analyte sensor, and modifying a predetermined sensor calibration schedule
based on the processed stability profile.

[0015]Embodiments also include a method comprising initializing an analyte
sensor, activating a timer associated with the analyte sensor, the timer
related to a stability profile of the analyte sensor, calibrating the
analyte sensor based on a time corresponding reference data based at
least in part on a predetermined calibration schedule including a
plurality time periods for performing calibration over the life of the
sensor, and modifying the calibration schedule to time shift the
plurality of time periods for performing calibration.

[0016]A method in certain embodiments include detecting an input value
associated with a reference data, verifying that an analyte sensor is
within its calibration stability duration, calibrating the analyte sensor
based on the detected input value, and time shifting the initiation of
the one or more subsequent scheduled calibration events for the analyte
sensor.

[0017]An apparatus in embodiments of the present disclosure includes one
or more processors, and a memory for storing instructions which, when
executed by the one or more processors, causes the one or more processors
to determine a stability profile of an in vivo analyte sensor in fluid
contact with a biological fluid by detecting the onset of a calibration
routine initialization within a predetermined time period, performing
stability analysis of the analyte sensor, and time shifting the
calibration routine initialization to start at a time period different
from the predetermined time period, to process the determined stability
profile in conjunction with calibration criteria for the analyte sensor,
and to modify a predetermined sensor calibration schedule based on the
processed stability profile.

[0018]Embodiments also include an apparatus comprising one or more
processors, and a memory for storing instructions which, when executed by
the one or more processors, causes the one or more processors to
initialize an analyte sensor, activate a timer associated with the
analyte sensor, the timer related to a stability profile of the analyte
sensor, calibrate the analyte sensor based on a time corresponding
reference data based at least in part on a predetermined calibration
schedule including a plurality time periods for performing calibration
over the life of the sensor, and modify the calibration schedule to time
shift the plurality of time periods for performing calibration.

[0019]Embodiments further include an apparatus comprising one or more
processors, and a memory for storing instructions which, when executed by
the one or more processors, causes the one or more processors to detect
an input value associated with a reference data, verify that an analyte
sensor is within its calibration stability duration, calibrate the
analyte sensor based on the detected input value, and time shift the
initiation of the one or more subsequent scheduled calibration events for
the analyte sensor.

[0020]These and other features, objects and advantages of the invention
will become apparent to those persons skilled in the art upon reading the
details of the invention as more fully described below.

[0022]A detailed description of various aspects, features and embodiments
of the present disclosure is provided herein with reference to the
accompanying drawings, which are briefly described below. The drawings
are illustrative and are not necessarily drawn to scale, with some
components and features being exaggerated for clarity. The drawings
illustrate various aspects or features of the present disclosure and may
illustrate one or more embodiment(s) or example(s) of the present
disclosure in whole or in part. A reference numeral, letter, and/or
symbol that is used in one drawing to refer to a particular element or
feature maybe used in another drawing to refer to a like element or
feature. Included in the drawings are the following:

[0023]FIG. 1 shows a block diagram of an embodiment of a data monitoring
and management system with which a sensor according to the present
disclosure is usable;

[0024]FIG. 2 shows a block diagram of an embodiment of the data processing
unit of the data monitoring and management system of FIG. 1;

[0025]FIG. 3 shows a block diagram of an embodiment of the
receiver/monitor unit of the data monitoring and management system of
FIG. 1;

[0026]FIG. 4 shows a schematic diagram of an embodiment of an analyte
sensor according to the present disclosure;

[0027]FIGS. 5A and 5B show perspective and cross sectional views,
respectively, of an embodiment of an analyte sensor according to the
present disclosure;

[0028]FIG. 6 is a flowchart illustrating dynamic sensor calibration
scheduling routine based on sensor stability profile in accordance with
one embodiment of the present disclosure; and

[0029]FIG. 7 is a flowchart illustrating another sensor calibration
scheduling routine in accordance with another embodiment of the present
disclosure.

DETAILED DESCRIPTION

[0030]Before the various embodiments of the present disclosure are
described, it is to be understood that the present disclosure is not
limited to particular embodiments described, as such may, of course,
vary. It is also to be understood that the terminology used herein is for
the purpose of describing particular embodiments only, and is not
intended to be limiting, since the scope of the present disclosure will
be limited only by the appended claims.

[0031]Where a range of values is provided, it is understood that each
intervening value, to the tenth of the unit of the lower limit unless the
context clearly dictates otherwise, between the upper and lower limit of
that range and any other stated or intervening value in that stated
range, is encompassed within the invention. The upper and lower limits of
these smaller ranges may independently be included in the smaller ranges
is also encompassed within the invention, subject to any specifically
excluded limit in the stated range. Where the stated range includes one
or both of the limits, ranges excluding either or both of those included
limits are also included in the invention.

[0032]It must be noted that as used herein and in the appended claims, the
singular forms "a", "an", and "the" include plural referents unless the
context clearly dictates otherwise.

[0033]As will be apparent to those of skill in the art upon reading this
disclosure, each of the individual embodiments described and illustrated
herein has discrete components and features which may be readily
separated from or combined with the features of any of the other several
embodiments without departing from the scope or spirit of the present
disclosure.

[0034]Generally, embodiments of the present disclosure relate to methods
and devices for detecting at least one analyte, such as glucose, in body
fluid. Embodiments relate to the continuous and/or automatic in vivo
monitoring of the level of one or more analytes using a continuous
analyte monitoring system that includes an analyte sensor for the in vivo
detection, of an analyte, such as glucose, lactate, and the like, in a
body fluid. Embodiments include wholly implantable analyte sensors and
analyte sensors in which only a portion of the sensor is positioned under
the skin and a portion of the sensor resides above the skin, e.g., for
contact to a control unit, transmitter, receiver, transceiver, processor,
etc. At least a portion of a sensor may be, for example, subcutaneously
positionable in a patient for the continuous or semi-continuous
monitoring of a level of an analyte in a patient's interstitial fluid.
For the purposes of this description, semi-continuous monitoring and
continuous monitoring will be used interchangeably, unless noted
otherwise. The sensor response may be correlated and/or converted to
analyte levels in blood or other fluids. In certain embodiments, an
analyte sensor may be positioned in contact with interstitial fluid to
detect the level of glucose, which detected glucose may be used to infer
the glucose level in the patient's bloodstream. Analyte sensors may be
insertable into a vein, artery, or other portion of the body containing
fluid. Embodiments of the analyte sensors of the subject invention may be
configured for monitoring the level of the analyte over a time period
which may range from minutes, hours, days, weeks, or longer.

[0035]FIG. 1 shows a data monitoring and management system such as, for
example, an analyte (e.g., glucose) monitoring system 100 in accordance
with certain embodiments. Embodiments of the subject invention are
further described primarily with respect to glucose monitoring devices
and systems, and methods of glucose detection, for convenience only and
such description is in no way intended to limit the scope of the
invention. It is to be understood that the analyte monitoring system may
be configured to monitor a variety of analytes instead of or in addition
to glucose, e.g., at the same time or at different times.

[0036]Analytes that may be monitored include, but are not limited to,
acetyl choline, amylase, bilirubin, cholesterol, chorionic gonadotropin,
creatine kinase (e.g., CK-MB), creatine, creatinine, DNA, fructosamine,
glucose, glutamine, growth hormones, hormones, ketone bodies, lactate,
oxygen, peroxide, prostate-specific antigen, prothrombin, RNA, thyroid
stimulating hormone, and troponin. The concentration of drugs, such as,
for example, antibiotics (e.g., gentamicin, vancomycin, and the like),
digitoxin, digoxin, drugs of abuse, theophylline, and warfarin, may also
be monitored. In those embodiments that monitor more than one analyte,
the analytes may be monitored at the same or different times.

[0037]The analyte monitoring system 100 includes a sensor 101, a data
processing unit 102 connectable to the sensor 101, and a primary receiver
unit 104 which is configured to communicate with the data processing unit
102 via a communication link 103. In certain embodiments, the primary
receiver unit 104 may be further configured to transmit data to a data
processing terminal 105 to evaluate or otherwise process or format data
received by the primary receiver unit 104. The data processing terminal
105 may be configured to receive data directly from the data processing
unit 102 via a communication link which may optionally be configured for
bi-directional communication. Further, the data processing unit 102 may
include a transmitter or a transceiver to transmit and/or receive data to
and/or from the primary receiver unit 104 and/or the data processing
terminal 105 and/or optionally the secondary receiver unit 106.

[0038]Also shown in FIG. 1 is an optional secondary receiver unit 106
which is operatively coupled to the communication link 103 and configured
to receive data transmitted from the data processing unit 102. The
secondary receiver unit 106 may be configured to communicate with the
primary receiver unit 104, as well as the data processing terminal 105.
The secondary receiver unit 106 may be configured for bi-directional
wireless communication with each of the primary receiver unit 104 and the
data processing terminal 105. As discussed in further detail below, in
certain embodiments the secondary receiver unit 106 may be a de-featured
receiver as compared to the primary receiver, i.e., the secondary
receiver may include a limited or minimal number of functions and
features as compared with the primary receiver unit 104. As such, the
secondary receiver unit 106 may include a smaller (in one or more,
including all, dimensions), compact housing or embodied in a device such
as a wrist watch, arm band, etc., for example. Alternatively, the
secondary receiver unit 106 may be configured with the same or
substantially similar functions and features as the primary receiver unit
104. The secondary receiver unit 106 may include a docking portion to be
mated with a docking cradle unit for placement by, e.g., the bedside for
nighttime monitoring, and/or a bi-directional communication device. A
docking cradle may recharge a power supply.

[0039]Only one sensor 101, data processing unit 102 and data processing
terminal 105 are shown in the embodiment of the analyte monitoring system
100 illustrated in FIG. 1. However, it will be appreciated by one of
ordinary skill in the art that the analyte monitoring system 100 may
include more than one sensor 101 and/or more than one data processing
unit 102, and/or more than one data processing terminal 105. Multiple
sensors may be positioned in a patient for analyte monitoring at the same
or different times. In certain embodiments, analyte information obtained
by a first positioned sensor may be employed as a comparison to analyte
information obtained by a second sensor. This may be useful to confirm or
validate analyte information obtained from one or both of the sensors.
Such redundancy may be useful if analyte information is contemplated in
critical therapy-related decisions.

[0040]The analyte monitoring system 100 may be a continuous monitoring
system or a semi-continuous monitoring system. In a multi-component
environment, each component may be configured to be uniquely identified
by one or more of the other components in the system so that
communication conflict may be readily resolved between the various
components within the analyte monitoring system 100. For example, unique
identification codes (IDs), communication channels, and the like, may be
used.

[0041]In certain embodiments, the sensor 101 is physically positioned in
and/or on the body of a user whose analyte level is being monitored. The
sensor 101 may be configured to continuously or semi-continuously sample
the analyte level of the user automatically (without the user initiating
the sampling), based on a programmed intervals such as, for example, but
not limited to, once every minute, once every five minutes and so on, and
convert the sampled analyte level into a corresponding signal for
transmission by the data processing unit 102. The data processing unit
102 is coupleable to the sensor 101 so that both devices are positioned
in or on the user's body, with at least a portion of the analyte sensor
101 positioned transcutaneously. The data processing unit 102 may include
a fixation element such as adhesive or the like to secure it to the
user's body. A mount (not shown) attachable to the user and mateable with
the data processing unit 102 may be used. For example, a mount may
include an adhesive surface. The data processing unit 102 performs data
processing functions, where such functions may include but are not
limited to, filtering and encoding of data signals, each of which
corresponds to a sampled analyte level of the user, for transmission to
the primary receiver unit 104 via the communication link 103. In one
embodiment, the sensor 101 or the data processing unit 102 or a combined
sensor/data processing unit may be wholly implantable under the skin
layer of the user. Exemplary embodiments of the analyte monitoring system
100 of FIG. 1 can be found in, among others, U.S. patent application Ser.
No. 12/698,124 incorporated herein by reference for all purposes.

[0042]In certain embodiments, the primary receiver unit 104 may include a
signal interface section including an RF receiver and an antenna that is
configured to communicate with the data processing unit 102 via the
communication link 103, and a data processing section for processing the
received data from the data processing unit 102 such as data decoding,
error detection and correction, data clock generation, data bit recovery,
etc., or any combination thereof.

[0043]In operation, the primary receiver unit 104 in certain embodiments
is configured to synchronize with the data processing unit 102 to
uniquely identify the data processing unit 102, based on, for example, an
identification information of the data processing unit 102, and
thereafter, to continuously or semi-continuously receive signals
transmitted from the data processing unit 102 associated with the
monitored analyte levels detected by the sensor 101. Referring again to
FIG. 1, the data processing terminal 105 may include a personal computer,
a portable computer such as a laptop or a handheld device (e.g., personal
digital assistants (PDAs), telephone such as a cellular phone (e.g., a
multimedia and Internet-enabled mobile phone such as an iPhone®, a
BlackBerry® mobile device or similar mobile device), mp3 player,
pager, a global positioning system (GPS) and the like), or drug delivery
device, each of which may be configured for data communication with the
receiver via a wired or a wireless connection. Additionally, the data
processing terminal 105 may further be connected to a data network (not
shown) for storing, retrieving, updating, and/or analyzing data
corresponding to the detected analyte level of the user.

[0044]The data processing terminal 105 may include an infusion device such
as an insulin infusion pump or the like, which may be configured to
administer insulin to patients, and which may be configured to
communicate with the primary receiver unit 104 for receiving, among
others, the measured analyte level. Alternatively, the primary receiver
unit 104 may be configured to integrate an infusion device therein so
that the primary receiver unit 104 is configured to administer insulin
(or other appropriate drug) therapy to patients, for example, for
administering and modifying basal profiles, as well as for determining
appropriate boluses for administration based on, among others, the
detected analyte levels received from the data processing unit 102. An
infusion device may be an external device or an internal device (wholly
implantable in a user).

[0045]In certain embodiments, the data processing terminal 105, which may
include an insulin pump, may be configured to receive the analyte signals
from the data processing unit 102, and thus, incorporate the functions of
the primary receiver unit 104 including data processing for managing the
patient's insulin therapy and analyte monitoring. In certain embodiments,
the communication link 103 as well as one or more of the other
communication interfaces shown in FIG. 1, may use one or more of: an RF
communication protocol, an infrared communication protocol, a
Bluetooth® enabled communication protocol, an 802.11x wireless
communication protocol, or an equivalent wireless communication protocol
which would allow secure, wireless communication of several units (for
example, per HIPPA requirements), while avoiding potential data collision
and interference.

[0046]FIG. 2 shows a block diagram of an embodiment of a data processing
unit of the data monitoring and detection system shown in FIG. 1. The
data processing unit 102 thus may include one or more of an analog
interface 201 configured to communicate with the sensor 101 (FIG. 1), a
user input 202, and a temperature measurement section 203, each of which
is operatively coupled to a processor 204 such as a central processing
unit (CPU). User input and/or interface components may be included or a
data processing unit may be free of user input and/or interface
components. In certain embodiments, one or more application-specific
integrated circuits (ASICs) may be used to implement one or more
functions or routines associated with the operations of the data
processing unit (and/or receiver unit) using for example one or more
state machines and buffers.

[0047]Further shown in FIG. 2 are a transmitter serial communication
section 205 and an RF transmitter 206, each of which is also operatively
coupled to the processor 204. The RF transmitter 206, in some
embodiments, may be configured as an RF receiver or an RF
transmitter/receiver, such as a transceiver, to transmit and/or receive
data signals. Moreover, a power supply 207, such as a battery, may also
be provided in the data processing unit 102 to provide the necessary
power for the data processing unit 102. Additionally, as can be seen from
the Figure, clock 208 may be provided to, among others, supply real time
information to the processor 204.

[0048]As can be seen in the embodiment of FIG. 2, the sensor 101 (FIG. 1)
includes four contacts, three of which are electrodes--work electrode (W)
210, guard contact (G) 211, reference electrode (R) 212, and counter
electrode (C) 213, each operatively coupled to the analog interface 201
of the data processing unit 102. In certain embodiments, each of the work
electrode (W) 210, guard contact (G) 211, reference electrode (R) 212,
and counter electrode (C) 213 may be made using a conductive material
that may be applied by, e.g., chemical vapor deposition (CVD), physical
vapor deposition, sputtering, reactive sputtering, printing, coating,
ablating (e.g., laser ablation), painting, dip coating, etching, and the
like.

[0049]In certain embodiments, a unidirectional input path is established
from the sensor 101 (FIG. 1) and/or manufacturing and testing equipment
to the analog interface 201 of the data processing unit 102, while a
unidirectional output is established from the output of the RF
transmitter 206 of the data processing unit 102 for transmission to the
primary receiver unit 104. In this manner, a data path is shown in FIG. 2
between the aforementioned unidirectional input and output via a
dedicated link 209 from the analog interface 201 to serial communication
section 205, thereafter to the processor 204, and then to the RF
transmitter 206. As such, in certain embodiments, via the data path
described above, the data processing unit 102 is configured to transmit
to the primary receiver unit 104 (FIG. 1), via the communication link 103
(FIG. 1), processed and encoded data signals received from the sensor 101
(FIG. 1). Additionally, the unidirectional communication data path
between the analog interface 201 and the RF transmitter 206 discussed
above allows for the configuration of the data processing unit 102 for
operation upon completion of the manufacturing process as well as for
direct communication for diagnostic and testing purposes.

[0050]The processor 204 may be configured to transmit control signals to
the various sections of the data processing unit 102 during the operation
of the data processing unit 102. In certain embodiments, the processor
204 also includes memory (not shown) for storing data such as the
identification information for the data processing unit 102, as well as
the data signals received from the sensor 101. The stored information may
be retrieved and processed for transmission to the primary receiver unit
104 under the control of the processor 204. Furthermore, the power supply
207 may include a commercially available battery.

[0051]The data processing unit 102 is also configured such that the power
supply section 207 is capable of providing power to the data processing
unit 102 for a minimum period of time, e.g., at least about one month,
e.g., at least about three months or more, of continuous operation. The
minimum may be after (i.e., in addition to), a period of time, e.g., up
to about eighteen months, of being stored in a low- or no-power
(non-operating) mode. In certain embodiments, this may be achieved by the
processor 204 operating in low power modes in the non-operating state,
for example, drawing no more than minimal current, e.g., approximately 1
μA of current or less. In certain embodiments, a manufacturing process
of the data processing unit 102 may place the data processing unit 102 in
the lower power, non-operating state (i.e., post-manufacture sleep mode).
In this manner, the shelf life of the data processing unit 102 may be
significantly improved. Moreover, as shown in FIG. 2, while the power
supply unit 207 is shown as coupled to the processor 204, and as such,
the processor 204 is configured to provide control of the power supply
unit 207, it should be noted that within the scope of the present
disclosure, the power supply unit 207 is configured to provide the
necessary power to each of the components of the data processing unit 102
shown in FIG. 2.

[0052]Referring back to FIG. 2, the power supply section 207 of the data
processing unit 102 in one embodiment may include a rechargeable battery
unit that may be recharged by a separate power supply recharging unit
(for example, provided in the receiver unit 104) so that the data
processing unit 102 may be powered for a longer period of usage time. In
certain embodiments, the data processing unit 102 may be configured
without a battery in the power supply section 207, in which case the data
processing unit 102 may be configured to receive power from an external
power supply source (for example, a battery, electrical outlet, etc.) as
discussed in further detail below.

[0053]Referring yet again to FIG. 2, a temperature measurement section 203
of the data processing unit 102 is configured to monitor the temperature
of the skin near the sensor insertion site. The temperature reading may
be used to adjust the analyte readings obtained from the analog interface
201.

[0054]The RF transmitter 206 of the data processing unit 102 may be
configured for operation in a certain frequency band, e.g., the frequency
band of 315 MHz to 322 MHz (or other suitable ranges), for example, in
the United States. (The frequency band may be the same or different
outside the United States. Further, in certain embodiments, the RF
transmitter 206 is configured to modulate the carrier frequency by
performing, e.g., Frequency Shift Keying and Manchester encoding, and/or
other protocol(s). In certain embodiments, the data transmission rate is
set for efficient and effective transmission. For example, in certain
embodiments the data transmission rate may be about 19,200 symbols per
second, with a minimum transmission range for communication with the
primary receiver unit 104.

[0055]Also shown is a leak detection circuit 214 coupled to the guard
electrode (G) 211 and the processor 204 in the data processing unit 102
of the data monitoring and management system 100. The leak detection
circuit 214 may be configured to detect leakage current in the sensor 101
to determine whether the measured sensor data are corrupt or whether the
measured data from the sensor 101 is accurate. Such detection may trigger
a notification to the user.

[0056]FIG. 3 shows a block diagram of an embodiment of a receiver/monitor
unit such as the primary receiver unit 104 of the data monitoring and
management system shown in FIG. 1. The primary receiver unit 104 may
include one or more of: a blood glucose test strip interface 301 for in
vitro testing, an RF receiver 302, an input 303, a temperature monitor
section 304, and a clock 305, each of which is operatively coupled to a
processing and storage section 307. The primary receiver unit 104 also
includes a power supply 306 operatively coupled to a power conversion and
monitoring section 308. Further, the power conversion and monitoring
section 308 is also coupled to the receiver processor 307. Moreover, also
shown are a receiver serial communication section 309, and an output 310,
each operatively coupled to the processing and storage unit 307. The
receiver may include user input and/or interface components or may be
free of user input and/or interface components.

[0057]In certain embodiments having a test strip interface 301, the
interface includes a glucose level testing portion to receive a blood (or
other body fluid sample) glucose test or information related thereto. For
example, the interface may include a test strip port to receive a glucose
test strip. The device may determine the glucose level of the test strip,
and optionally display (or otherwise notice) the glucose level on the
output 310 of the primary receiver unit 104. Any suitable test strip may
be employed, e.g., test strips that only require a very small amount
(e.g., one microliter or less, e.g., 0.5 microliter or less, e.g., 0.1
microliter or less), of applied sample to the strip in order to obtain
accurate glucose information, e.g. FreeStyle® and Precision®
blood glucose test strips from Abbott Diabetes Care Inc.

[0058]Glucose information obtained by the in vitro glucose testing device
may be used for a variety of purposes, computations, etc. For example,
the information may be used to calibrate sensor 101 (however, calibration
of the subject sensors may not be necessary), confirm results of the
sensor 101 to increase the confidence thereof (e.g., in instances in
which information obtained by sensor 101 is employed in therapy related
decisions), etc. Exemplary blood glucose monitoring systems are
described, e.g., in U.S. Pat. Nos. 6,071,391; 6,120,676; 6,338,790; and
6,616,819; and in U.S. application Ser. Nos. 11/282,001; and 11/225,659,
the disclosures of which are herein incorporated by reference. Glucose
monitoring systems that allow for sample extraction from sites other than
the finger and/or that can operate using small samples of blood, have
been developed. (See, e.g., U.S. Pat. Nos. 6,120,676, 6,591,125, and
7,299,082, the disclosures of which are herein incorporated by
reference). Typically, about one μL or less of sample may be required
for the proper operation of these devices, which enables glucose testing
with a sample of blood obtained from the surface of a palm, a hand, an
arm, a thigh, a leg, the torso, or the abdomen. Even though less painful
than the finger stick approach, these other sample extraction methods are
still inconvenient and may also be somewhat painful.

[0059]The RF receiver 302 is configured to communicate, via the
communication link 103 (FIG. 1) with the RF transmitter 206 of the data
processing unit 102, to receive encoded data signals from the data
processing unit 102 for, among others, signal mixing, demodulation, and
other data processing. The input 303 of the primary receiver unit 104 is
configured to allow the user to enter information into the primary
receiver unit 104 as needed. In one aspect, the input 303 may include
keys of a keypad, a touch-sensitive screen, and/or a voice-activated
input command unit, and the like. The temperature monitor section 304 is
configured to provide temperature information of the primary receiver
unit 104 to the receiver processing and storage unit 307, while the clock
305 provides, among others, real time information to the receiver
processing and storage unit 307.

[0060]Each of the various components of the primary receiver unit 104
shown in FIG. 3 is powered by the power supply 306 (and/or other power
supply) which, in certain embodiments, includes a battery. Furthermore,
the power conversion and monitoring section 308 is configured to monitor
the power usage by the various components in the primary receiver unit
104 for effective power management and may alert the user, for example,
in the event of power usage which renders the primary receiver unit 104
in sub-optimal operating conditions. An example of such sub-optimal
operating condition may include, for example, operating the vibration
output mode (as discussed below) for a period of time thus substantially
draining the power supply 306 while the processing and storage unit 307
(thus, the primary receiver unit 104) is turned on. Moreover, the power
conversion and monitoring section 308 may additionally be configured to
include a reverse polarity protection circuit such as a field effect
transistor (FET) configured as a battery activated switch.

[0061]The serial communication section 309 in the primary receiver unit
104 is configured to provide a bi-directional communication path from the
testing and/or manufacturing equipment for, among others, initialization,
testing, and configuration of the primary receiver unit 104. Serial
communication section 309 can also be used to upload data to a computer,
such as time-stamped blood glucose data. The communication link with an
external device (not shown) can be made, for example, by cable, infrared
(IR) or RF link. The output 310 of the primary receiver unit 104 is
configured to provide, among others, a graphical user interface (GUI)
such as a liquid crystal display (LCD) for displaying information.
Additionally, the output 310 may also include an integrated speaker for
outputting audible signals as well as to provide vibration output as
commonly found in handheld electronic devices, such as mobile telephones,
pagers, etc. In certain embodiments, the primary receiver unit 104 also
includes an electro-luminescent lamp configured to provide backlighting
to the output 310 for output visual display in dark ambient surroundings.

[0062]Referring back to FIG. 3, the primary receiver unit 104 may also
include a storage section such as a programmable, non-volatile memory
device as part of the processing and storage unit 307, or provided
separately in the primary receiver unit 104, operatively coupled to the
processor. The processing and storage unit 307 may be configured to
perform Manchester decoding (or other protocol(s)) as well as error
detection and correction upon the encoded data signals received from the
data processing unit 102 via the communication link 103 (FIG. 1).

[0063]In further embodiments, the data processing unit 102 and/or the
primary receiver unit 104 and/or the secondary receiver unit 106 (FIG.
1), and/or the data processing terminal/infusion section 105 may be
configured to receive the blood glucose value from a wired connection or
wirelessly over a communication link from, for example, a blood glucose
meter. In further embodiments, a user manipulating or using the analyte
monitoring system 100 (FIG. 1) may manually input the blood glucose value
using, for example, a user interface (for example, a keyboard, keypad,
voice commands, and the like) incorporated in the one or more of the data
processing unit 102, the primary receiver unit 104, secondary receiver
unit 106, or the data processing terminal/infusion section 105.

[0064]In certain embodiments, the data processing unit 102 (FIG. 1) is
configured to detect the current signal from the sensor 101 (FIG. 1) and
optionally the skin and/or ambient temperature near the sensor 101, which
may be preprocessed by, for example, the data processing unit processor
204 (FIG. 2) and transmitted to the receiver unit (for example, the
primary receiver unit 104 (FIG. 1)) at least at a predetermined time
interval, such as for example, but not limited to, once per minute, once
every two minutes, once every five minutes, or once every ten minutes.
Additionally, the data processing unit 102 may be configured to perform
sensor insertion detection and data quality analysis, information
pertaining to which may also transmitted to the receiver unit 104
periodically at the predetermined time interval. In turn, the receiver
unit 104 may be configured to perform, for example, skin temperature
compensation as well as calibration of the sensor data received from the
data processing unit 102.

[0065]Additional detailed descriptions are provided in U.S. Pat. Nos.
5,262,035; 5,264,104; 5,262,305; 5,320,715; 5,593,852; 6,103,033;
6,134,461; 6,175,752; 6,560,471; 6,579,690; 6,605,200; 6,654,625;
6,746,582; and 6,932,894; and in U.S. Published Patent Application Nos.
2004/0186365, the disclosures of which are herein incorporated by
reference.

[0067]The sensor may be wholly implantable in a user or may be configured
so that only a portion is positioned within (internal) a user and another
portion outside (external) a user. For example, the sensor 400 may
include a portion positionable above a surface of the skin 410, and a
portion positioned below the skin. In such embodiments, the external
portion may include contacts (connected to respective electrodes of the
second portion by traces) to connect to another device also external to
the user such as a transmitter unit. While the embodiment of FIG. 4 shows
three electrodes side-by-side on the same surface of base 404, other
configurations are contemplated, e.g., fewer or greater electrodes, some
or all electrodes on different surfaces of the base or present on another
base, some or all electrodes stacked together, some or all electrodes
twisted together (e.g., an electrode twisted around or about another or
electrodes twisted together), electrodes of differing materials and
dimensions, etc.

[0068]In other embodiments, the sensor is a self-powered sensor, such as
the sensor described in U.S. patent application Ser. No. 12/393,921,
incorporated herein by reference.

[0069]FIG. 5A shows a perspective view of an embodiment of an
electrochemical analyte sensor 500 of the present disclosure having a
first portion (which in this embodiment may be characterized as a major
or body portion) positionable above a surface of the skin 510, and a
second portion (which in this embodiment may be characterized as a minor
or tail portion) that includes an insertion tip 530 positionable below
the skin, e.g., penetrating through the skin and into, e.g., the
subcutaneous space 520, in contact with the user's biofluid such as
interstitial fluid. Contact portions of a working electrode 501, a
reference electrode 502, and a counter electrode 503 are positioned on
the portion of the sensor 500 situated above the skin surface 510.
Working electrode 501, a reference electrode 502, and a counter electrode
503 are shown at the second section and particularly at the insertion tip
530. Traces may be provided from the electrode at the tip to the contact,
as shown in FIG. 5A. It is to be understood that greater or fewer
electrodes may be provided on a sensor. For example, a sensor may include
more than one working electrode and/or the counter and reference
electrodes may be a single counter/reference electrode, etc.

[0070]FIG. 5B shows a cross sectional view of a portion of the sensor 500
of FIG. 5A. The electrodes 501, 502 and 503 of the sensor 500 as well as
the substrate and the dielectric layers are provided in a layered
configuration or construction. For example, as shown in FIG. 5B, in one
aspect, the sensor 500 (such as the sensor 101 FIG. 1), includes a
substrate layer 504, and a first conducting layer 501 such as carbon,
gold, etc., disposed on at least a portion of the substrate layer 504,
and which may provide the working electrode. Also shown disposed on at
least a portion of the first conducting layer 501 is a sensing component
or layer 508, discussed in greater detail below. The area of the
conducting layer covered by the sensing layer is herein referred to as
the active area. A first insulation layer such as a first dielectric
layer 505 is disposed or layered on at least a portion of the first
conducting layer 501, and further, a second conducting layer 502 may be
disposed or stacked on top of at least a portion of the first insulation
layer (or dielectric layer) 505, and which may provide the reference
electrode.

[0071]In one aspect, conducting layer 502 may include a layer of
silver/silver chloride (Ag/AgCl), gold, etc. A second insulation layer
506 such as a dielectric layer in one embodiment may be disposed or
layered on at least a portion of the second conducting layer 509.
Further, a third conducting layer 503 may provide the counter electrode
503. It may be disposed on at least a portion of the second insulation
layer 506. Finally, a third insulation layer 507 may be disposed or
layered on at least a portion of the third conducting layer 503. In this
manner, the sensor 500 may be layered such that at least a portion of
each of the conducting layers is separated by a respective insulation
layer (for example, a dielectric layer). The embodiment of FIGS. 5A and
5B show the layers having different lengths. Some or all of the layers
may have the same or different lengths and/or widths.

[0072]In addition to the electrodes, sensing layer and dielectric layers,
sensor 500 may also include a temperature probe, a mass transport
limiting layer, a biocompatible layer, and/or other optional components
(none of which are illustrated). Each of these components enhances the
functioning of and/or results from the sensor.

[0073]Substrate 504 may be formed using a variety of non-conducting
materials, including, for example, polymeric or plastic materials and
ceramic materials. (It is to be understood that substrate includes any
dielectric material of a sensor, e.g., around and/or in between
electrodes of a sensor such as a sensor in the form of a wire wherein the
electrodes of the sensor are wires that are spaced-apart by a substrate).

[0074]Although the sensor substrate, in at least some embodiments, has
uniform dimensions along the entire length of the sensor, in other
embodiments, the substrate has a distal end or tail portion and a
proximal end or body portion with different widths, respectively, as
illustrated in FIG. 5A. In these embodiments, the distal end 530 of the
sensor may have a relatively narrow width. For in vivo sensors which are
implantable into the subcutaneous tissue or another portion of a
patient's body, the narrow width of the distal end of the substrate may
facilitate the implantation of the sensor. Often, the narrower the width
of the sensor, the less pain the patient will feel during implantation of
the sensor and afterwards.

[0075]For subcutaneously implantable sensors which are designed for
continuous or semi-continuous monitoring of the analyte during normal
activities of the patient, a tail portion or distal end of the sensor
which is to be implanted into the patient may have a width of about 2 mm
or less, e.g., about 1 mm or less, e.g., about 0.5 mm or less, e.g.,
about 0.25 mm or less, e.g., about 0.15 or less. However, wider or
narrower sensors may be used. The proximal end of the sensor may have a
width larger than the distal end to facilitate the connection between the
electrode contacts and contacts on a control unit, or the width may be
substantially the same as the distal portion.

[0076]Electrodes 501, 502 and 503 are formed using conductive traces
disposed on the substrate 504. These conductive traces may be formed over
a smooth surface of the substrate or within channels formed by, for
example, embossing, indenting or otherwise creating a depression in the
substrate. The conductive traces may extend most of the distance along a
length of the sensor, as illustrated in FIG. 5A, although this is not
necessary. For implantable sensors, particularly subcutaneously
implantable sensors, the conductive traces typically may extend close to
the tip of the sensor to minimize the amount of the sensor that must be
implanted.

[0077]The conductive traces may be formed on the substrate by a variety of
techniques, including, for example, photolithography, screen printing, or
other impact or non-impact printing techniques. The conductive traces may
also be formed by carbonizing conductive traces in an organic (e.g.,
polymeric or plastic) substrate using a laser. A description of some
exemplary methods for forming the sensor is provided in U.S. patents and
applications noted herein, including U.S. Pat. Nos. 5,262,035, 6,103,033,
6,175,752; and 6,284,478, the disclosures of which are herein
incorporated by reference.

[0078]Certain embodiments include a Wired Enzyme® sensing layer (such
as used in the FreeStyle Navigator® continuous glucose monitoring
system by Abbott Diabetes Care Inc.) that works at a gentle oxidizing
potential, e.g., a potential of about +40 mV. This sensing layer uses an
osmium (Os)-based mediator designed for low potential operation and is
stably anchored in a polymeric layer. Accordingly, in certain embodiments
the sensing element is redox active component that includes (1)
Osmium-based mediator molecules attached by stable (bidente) ligands
anchored to a polymeric backbone, and (2) glucose oxidase enzyme
molecules. These two constituents are crosslinked together.

[0079]Examples of sensing layers that may be employed are described in
U.S. patents and applications noted herein, including, e.g., in U.S. Pat.
Nos. 5,262,035, 5,264,104, 5,543,326, 6,605,200, 6,605,201, 6,676,819,
and 7,299,082, the disclosures of which are herein incorporated by
reference.

[0080]Regardless of the particular components that make up a given sensing
layer, a variety of different sensing layer configurations may be used.
In certain embodiments, the sensing layer covers the entire working
electrode surface, e.g., the entire width of the working electrode
surface. In other embodiments, only a portion of the working electrode
surface is covered by the sensing layer, e.g., only a portion of the
width of the working electrode surface. Alternatively, the sensing layer
may extend beyond the conductive material of the working electrode. In
some cases, the sensing layer may also extend over other electrodes,
e.g., over the counter electrode and/or reference electrode (or
counter/reference is provided), and may cover all or only a portion
thereof.

[0081]Calibration, when an electrochemical glucose sensor is used,
generally involves converting the raw current signal (nA) into a glucose
concentration (mg/dL). One way in which this conversion is achieved is by
relating or equating the raw analyte signal with a calibration
measurement (i.e., with a reference measurement), and obtaining a
conversion factor (raw analyte signal/reference measurement value). This
relationship is often referred to as the sensitivity of the sensor,
which, once determined, may then be used to convert sensor signals to
calibrated analyte concentration values, e.g., via simple division (raw
analyte signal/sensitivity=calibrated analyte concentration). For
example, a raw analyte signal of 10 nA could be associated with a
calibration analyte concentration of 100 mg/dL, and thus, a subsequent
raw analyte signal of 20 nA could be converted to an analyte
concentration of 200 mg/dL, as may be appropriate for a given analyte,
such as glucose, for example.

[0082]There are many ways in which the conversion factor may be obtained.
For example, the sensitivity factor can be derived from a simple average
of multiple analyte signal/calibration measurement data pairs, or from a
weighted average of multiple analyte signal/calibration measurement data
pairs. Further by way of example, the sensitivity may be modified based
on an empirically derived weighting factor, or the sensitivity may be
modified based on the value of another measurement, such as temperature.
It will be appreciated that any combination of such approaches, and/or
other suitable approaches, is contemplated herein.

[0083]Exemplary calibration protocols, routines and techniques are
described, for example, in U.S. Pat. No. 7,299,082, U.S. patent
application Ser. No. 11/537,991 filed Oct. 2, 2006, and in U.S. patent
application Ser. No. 12/363,712 filed Jan. 30, 2009, the disclosure of
each of which are herein incorporated by reference for all purposes.

[0084]In one embodiment, the calibration information or routine is
programmed or is programmable into software of the monitoring system,
e.g., into one or more processors. For example, calibration of sensor
signal may be implemented using suitable hardware/software of the system.

[0085]In one aspect of the present disclosure, a dynamic sensor
calibration schedule for analyte monitoring system is provided. More
specifically, in one aspect, based on the stability profile of the
sensor, the baseline or predetermined calibration time periods may be
dynamically modified, providing convenience and improved functionality to
the user of the analyte monitoring system.

[0086]More specifically, in accordance with aspects of the present
disclosure, self initiated in vitro blood glucose tests performed
(whether to confirm the in vivo sensor accuracy, for example, in response
to a calibration prompt provided by the system, or whether performed
independent of a scheduled calibration event by the user to, for example,
determine a correction insulin bolus dose) may be used to calibrate the
in vivo analyte sensor in conjunction with an analysis of the sensor
profile, such as, for example, the stability profile of the analyte
sensor.

[0087]That is, in one aspect, a calibration stability duration or a
"stability profile" may be predetermined or assigned to the analyte
sensor during the various time periods of the sensor usage/life. For
example, in one aspect, after initialization of the sensor at the
beginning of its usage, the first 12 hours of the sensor usage (measured
for example, from the sensor positioning/insertion time) may be
associated with a two hour window of sensor calibration stability
duration. Thereafter, the next 12 hours (or, the time period spanning 12
to 24 hours measured from the initial sensor insertion/initialization or
positioning) may be associated with a calibration stability duration of 6
hours, during which it is determined that the analyte sensor property is
deemed to be stable (for example, for purposes of performing sensor
calibration). Returning to the example above, the subsequent 48 hour
period measured from the initial sensor insertion (that is, the 24 hour
to 72 hour time period from the sensor insertion) may be associated with
a calibration stability duration of a 12 hour period (during which, the
sensor is considered to be sufficiently stable for performing
calibration), and thereafter, the following 48 hour period (that is, the
time period from the 72 hour to 120 hours measured from the initial
sensor insertion/positioning and initialization for use) is associated in
one embodiment, with a calibration stability duration of a 24 hour time
window, during which, the sensor is considered to be sufficiently stable
for performing calibration routine.

[0088]In another embodiment, the first 6 hours of sensor usage may be
associated with a two hour window of sensor calibration stability
duration, the next 18 hours of sensor life associated with a calibration
stability duration of 8 hours, and so on. In still a further embodiment,
the calibration stability duration for each 12 hour period is increased
linearly, so that the first 12 hours of sensor life is associated with a
2 hour calibration stability duration, the next 12 hours of sensor life
associated with a 4 hour calibration stability duration, the following 12
hours of sensor life associated with a 6 hour calibration stability
duration and so on. Other calibration stability durations are also
contemplated within the scope of the present disclosure including those
which increments the stability duration in a nonlinear fashion and so on.

[0089]In this manner, in one aspect, the analyte monitoring system (for
example, the receiver unit of the monitoring system) may be configured to
monitor the time period of each sensor calibration event, for example,
determined from the initial sensor insertion/positioning and
initialization for use, and when it is determined that the system has not
received a current in vitro blood glucose measurement for calibration
during the calibration stability duration associated with the one or more
time periods of sensor wear, the system may be configured to prompt the
user or the patient to perform a blood glucose test to execute or
initiate the in vivo sensor calibration routine. Detailed description of
signal processing related to sensor initialization, signal filtering, and
processing can be found in U.S. Pat. Nos. 6,175,752, 6,560,471, and in
U.S. patent application Ser. No. 12/152,649 filed May 14, 2008,
disclosure of each of which are incorporated herein by reference for all
purposes.

[0090]Upon successfully completing the executed calibration routine, in
one aspect, the monitoring system may be configured to reset or modify
the next or subsequent scheduled calibration event based on the
successful calibration routine performed, rather than maintaining the
baseline or pre-programmed calibration schedule for calibrating the
sensor. Moreover, when the user or the patient performs an in vitro blood
glucose test and inputs the glucose information to the monitoring system
(for example, the receiver unit) to perform sensor calibration even
though the calibration request based on the predetermined calibration
schedule has not yet been triggered, the results from the performed blood
glucose test in one embodiment may be used to perform sensor calibration,
and thereafter, extending the calibration stability duration or profile
in view of the self or manually initiated blood glucose measurement
provided to the monitoring system.

[0091]In one aspect, a timer or clock may be provided on the user
interface (or display) of the receiver unit to provide a visual, tactile,
or audible indication of the subsequent or upcoming scheduled calibration
and the associated calibration stability duration. Such indication may
include one or more of an icon, a graphical representation, a video
graphics, a two-dimensional representation, an alphanumeric display, a
sound, a predetermined vibration of the device (for example, the receiver
unit), or one or more combinations thereof. With the ability to view the
upcoming scheduled calibration time period and the corresponding
calibration stability duration, in one aspect, the user of the monitoring
system may dynamically modify the predetermined calibration schedule to
tailor the calibration events to be more convenient to the user.

[0092]For example, prior to going to bed at night, the user may review the
calibration stability duration information provided on the receiver unit
of the monitoring system, for example, that the user is in the 12 hour
time period for calibration stability duration, of which, 8 hours have
already elapsed. In such a case, in one aspect, the receiver unit of the
monitoring system, for example, may generate and output a calibration
prompt or alarm after 4 hours have elapsed (that is, since 8 hours has
elapsed, and the user is preparing to go to bed), the pre-programmed
alarm or notification associated with the calibration is programmed to be
output 4 hours after the user goes to bed. With this information, since
it is inconvenient to wake up or get up after 4 hours of sleeping to
perform an in vitro blood glucose test for in vivo sensor calibration,
the user may self initiate the in vitro blood glucose test prior to going
to bed and perform sensor calibration using the data from the blood
glucose test.

[0093]Then, the associated calibration stability duration may be extended
to a 12 hour time period from when the in vitro blood glucose test was
performed (or when the user is going to sleep). In this case, in one
aspect, the user will likely not be inconvenienced when attempting to
maintain the calibration schedule of the analyte sensor, and further,
maintaining the integrity of the analyte monitoring system so as to
ensure that the sensor is properly calibrated to provide accurate, real
time information associated with the monitored analyte levels.

[0094]Referring now to the Figures, FIG. 6 is a flowchart illustrating
dynamic sensor calibration based on sensor stability profile in
accordance with one embodiment of the present disclosure. Referring to
FIG. 6, when the analyte sensor is transcutaneously positioned such that
at least a portion is in fluid contact with the analyte (for example,
interstitial fluid) of a subject, an initialization routine is executed
(by, for example, one or more transmitter unit/data processing unit 102
(FIG. 1) or the receiver unit 104 (FIG. 1) (610). Also, a clock or a
timing device is activated to maintain timing information of the sensor
usage from initialization in the analyte monitoring system (620).

[0095]In one aspect, the clock or timing device may be triggered or
started with the initialization of the sensor, and each sensor signal or
data (corresponding to the monitored analyte level) is associated with
corresponding time information based on the time data from the clock or
timing device. In the case where the clock or timing device is in the
data processing unit 102 (FIG. 1), in one embodiment, the data packet
from the transmitter unit may be configured to including the timing
information (such as a time and/or date stamp) associated with each
processed sensor data for transmission to the receiver unit 104 (FIG. 1).
In another embodiment, the clock or timing device may be maintained in
the receiver unit 104 (FIG. 1), such that when the sensor data is
received from the data processing unit 102 (FIG. 1), the receiver unit
104 may be configured to generate and associate timing information for
each received sensor data for further processing, storage and
transmission to one or more remote locations (such as over a data
network, or using a local connection to a host or personal computer with
software suitable for processing and analyzing glucose information for
the patient or the subject). In still a further aspect, the clock or
timing device may be maintained or functional in both the data processing
unit and the receiver unit, and, may be used to time synchronize the two
components, in addition to maintaining timing information associated with
the sensor data.

[0096]As discussed above, each time period or segment of the sensor usage
may be associated with a corresponding predetermined calibration
stability duration. For example, the first 12 hours of the sensor usage
measured from the sensor initialization may be associated with a two hour
calibration stability duration or window. Accordingly, depending upon the
clock or timing device information, the corresponding calibration
stability duration is retrieved (for example, from storage device such a
memory device). The analyte monitoring system generates and outputs a
calibration prompt to the user to perform sensor calibration when the
calibration stability duration expiration is approaching (for example,
within 30 minutes of the two hour duration expiration), and further, the
analyte monitoring system monitors for any data input associated with in
vitro blood glucose measurements independent of calibration requests that
are received, for example, within the calibration stability duration.

[0097]In one aspect, an output indicator associated with the calibration
stability duration may be generated and output to the user. For example,
the display on the receiver unit 104 (FIG. 1) may be configured to
illustrate an icon, a graphical indicator or a numerical indicator, or
one or more combinations, which indicate the time period remaining for
the particular calibration stability duration that is retrieved and
associated with the sensor usage period. Such indicator would assist the
user to modify user behavior knowing that a calibration prompt or request
from the monitoring system is approaching, especially when the user will
not have ready access to the calibration tool, such as in vitro blood
glucose meter device to determine the reference blood glucose measurement
so that the in vivo sensor calibration may be performed.

[0098]Furthermore, in the case where the user is planning to go to sleep
within a couple of hours, and the user is aware that the monitoring
system calibration request is approaching in approximately 4 hours (which
may be in the middle of the night when the user will likely be asleep),
the user decides to perform the sensor calibration prior to going to
sleep, so that the next schedule calibration for the analyte sensor may
be rescheduled to a time beyond the initially approaching time period of
4 hours (such as, for example, in the morning). In this manner, the user
may not be inconvenienced with any alarm or notification associated with
the scheduled calibration prompt from the analyte monitoring system, for
example, while the user is asleep.

[0099]Referring back to FIG. 6, when the user performs an in vitro blood
glucose measurement and enters that information into the analyte
monitoring system (independent of the calibration schedule), assuming the
blood glucose measurement can be used to successfully calibrate the
sensor, the received blood glucose (or reference) measurement is
accepted, and the sensor is calibrated based at least in part on the
received blood glucose measurement (630), and the subsequent scheduled
calibration time is automatically or semi-automatically (based on user
confirmation) updated or otherwise modified to take into account the
successful sensor calibration event (640). In other words, in embodiments
of the present disclosure, when acceptable reference blood glucose
measurement or calibration information (for example, from an in vitro
blood glucose test) is received during the predetermined calibration time
window for a particular scheduled calibration time period, the received
glucose measurement may be accepted and used to calibrate the sensor, and
the user is not thereafter prompted to perform another calibration during
that predetermined calibration time window. In this manner, over the
course of the sensor life (for example, five days, seven days or longer
or shorter), any in vitro blood glucose measurements that the user
performs (for reasons unrelated to sensor calibration requirement) and
enters into the analyte monitoring system may be accepted as reference
data for purposes of sensor calibration.

[0100]Embodiments further include dynamically shifting the scheduled time
periods for performing the calibration (i.e., the calibration schedule
for the particular sensor during in vivo use) such that, when a
successful calibration has been performed, any remaining or subsequent
scheduled calibration event is modified based on the successful
calibration event. For example, referring back to FIG. 6, updating the
calibration schedule (640) may include time shifting the subsequent
scheduled calibration events so that they remain temporally spaced
relative to each other, but are shifted in time based on the successful
calibration performed.

[0101]FIG. 7 is a flowchart illustrating another sensor calibration
scheduling routine in accordance with another embodiment of the present
disclosure. Referring to FIG. 7, in certain embodiments, a sensor life
time period is segmented or divided into a plurality of time periods, and
a sensor calibration schedule is provided for the sensor (710) over the
sensor life (such as a seven day time period for a sensor with a seven
day sensor life). The sensor system is also provided with a calibration
schedule to calibrate the sensor over the sensor life. For example, upon
sensor insertion at the start of the in vivo use, the sensor system may
be programmed to prompt or notify the user to calibrate the sensor during
certain times over the life of the sensor. By way of a non-limiting
example, for the sensor with a seven day sensor life, the sensor system
(e.g., receiver unit 104 (FIG. 1), may be programmed or programmable to
prompt the user to enter or provide calibration data (such as the results
of an in vitro blood glucose measurement) to calibrate the sensor at
certain time intervals such as once every 24 hours (measured from time of
sensor insertion), or progressively increased, such as the initial
calibration scheduled at or around 6 hours from initial insertion,
thereafter the second calibration scheduled at 12 hours from the initial
scheduled calibration (or 18 hours measured from the initial sensor
insertion), and the third calibration scheduled at 48 hours measured from
the initial sensor insertion (or 30 hours from the second scheduled
calibration), and so on. Each segment of the plurality of time periods of
the sensor life time period may or may not coincide with the scheduled
calibration time periods or events.

[0102]Referring to FIG. 7, each of the plurality of time periods of the
sensor life is assigned a respective calibration stability time window
(720). That is, embodiments include a first time period segment which
includes the first 6 hours of the sensor use measured from the sensor
insertion and during which the calibration stability window assigned may
be a two hour period. The second time period segment may be assigned or
defined as the subsequent 12 hours following the first time period of the
sensor life, and assigned a calibration stability of six hour period.
Referring to FIG. 7, when a calibration data (such as, for example, the
results of an in vitro blood glucose measurement) is entered or provided
to the sensor system by the user or from another medical device such as a
blood glucose meter, it is determined whether the time of receipt of the
calibration data falls within the assigned or determined calibration
stability window (730).

[0103]If the time of receipt of the calibration data falls within the
determined calibration stability window, then the calibration routine
proceeds with the sensor calibration procedure (740), and thereafter if
the calibration was successful, subsequent scheduled sensor calibration
events are shifted based on when the successful sensor calibration is
performed (750). That is, when the successful calibration occurred two
hours prior to the scheduled sensor calibration, and the subsequent
segmented sensor life time period is associated with a 12 hour stability
window, the subsequent or the next scheduled calibration time is
accordingly adjusted and the 12 hour stability window is updated to
provide the user with a modified or updated stability time window, such
that the 12 hour stability window is initiated or measured from the
successful calibration event (e.g., two hours prior to the scheduled
sensor calibration discussed above).

[0104]In the event the calibration procedure (740) is deemed unsuccessful,
the routine may return to the beginning as shown in the figure. In
certain embodiments, if the calibration procedure (740) is unsuccessful,
the routine may not shift the subsequent scheduled sensor calibration
events, and the next scheduled calibration time is not adjusted, i.e. the
calibration routine continues as though the received calibration data was
never received. In still certain embodiments, if the calibration
procedure (740) is unsuccessful, the system may trigger an alarm or alert
to inform or instruct the user to provide a new calibration data.

[0105]In this manner, embodiments include dynamically modifying the
scheduled sensor calibration based on, for example, a predetermined or
assigned sensor stability profile or time window which may be determined
or modified in real time based on the analyte sensor signal response (for
example, based on the signal stability profile), and/or based on one or
more predetermined stability time window that is empirically or
analytically determined for each sensor having a particular sensor life,
or for each sensor in each manufactured sensor lot based on a particular
manufacturing process. Moreover, in accordance with embodiments of the
present disclosure, a convenient and robust sensor system is provided
which does not require a strict adherence to prescheduled sensor
calibration time periods and which may be modified during in vivo use.

[0106]In the manner described above, in one aspect of the present
disclosure, dynamic variation or modification to the sensor calibration
schedule based at least in part on the sensor stability profile is
provided. While specific example values for the calibration stability
duration for the different time periods of the sensor life is described
above, within the scope of the present disclosure, the values provided
above are solely for exemplary purposes, and are not intended to limit
the scope of the various embodiments described herein. For example, the
calibration stability duration for the first 12 hours of sensor life may
be greater than two hours (such as four hours, five hours or more),
depending upon, for example, the manufacturing conditions and/or
tolerance of the analyte sensor and variation one or more parameters
during the manufacturing process.

[0107]Additionally, in a further aspect of the present disclosure, the
predetermined calibration stability duration for one or more of the time
periods for the sensor may be associated with the sensor shelf life, such
that older sensors (that have earlier manufacturing date) have greater
sensor drift as compared to those sensors that were more recently
manufactured. In this aspect, the associated calibration stability
duration may be associated with the date of manufacture of the sensor,
with, for example, the stability duration decreasing in range or
configured to be tightened if the time period measured from the sensor
manufacturing to when the sensor is being used (current time information
determined by the data processing unit and/or the receiver unit) is
greater than a predetermined time period.

[0108]The analyte monitoring systems may include an optional alarm system
that, e.g., based on information from a processor, warns the patient of a
potentially detrimental condition of the analyte. For example, if glucose
is the analyte, an alarm system may warn a user of conditions such as
hypoglycemia and/or hyperglycemia and/or impending hypoglycemia, and/or
impending hyperglycemia. An alarm system may be triggered when analyte
levels approach, reach or exceed a threshold value. An alarm system may
also, or alternatively, be activated when the rate of change, or
acceleration of the rate of change, in analyte level increase or decrease
approaches, reaches or exceeds a threshold rate or acceleration. A system
may also include system alarms that notify a user of system information
such as system initialization, sensor initialization, sensor replacement,
battery condition, sensor calibration, sensor dislodgment, sensor
malfunction, etc. Alarms may be, for example, auditory and/or visual.
Other sensory-stimulating alarm systems may be used including alarm
systems which heat, cool, vibrate, or produce a mild electrical shock
when activated.

[0109]Embodiments of the present disclosure also include sensors used in
sensor-based drug delivery systems. The system may provide a drug to
counteract the high or low level of the analyte in response to the
signals from one or more sensors. Alternatively, the system may monitor
the drug concentration to ensure that the drug remains within a desired
therapeutic range. The drug delivery system may include one or more
(e.g., two or more) sensors, a processing unit such as a transmitter, a
receiver/display unit, and a drug administration system. In some cases,
some or all components may be integrated in a single unit. A sensor-based
drug delivery system may use data from the one or more sensors to provide
necessary input for a control algorithm/mechanism to adjust the
administration of drugs, e.g., automatically or semi-automatically. As an
example, a glucose sensor may be used to control and adjust the
administration of insulin from an external or implanted insulin pump.

[0110]One embodiment may include a method of determining a stability
profile of an in vivo analyte sensor in fluid contact with a biological
fluid, processing the determined stability profile in conjunction with
calibration criteria for the analyte sensor, and modifying a
predetermined sensor calibration schedule based on the processed
stability profile.

[0111]In one aspect, determining the stability profile may include
detecting the onset of a calibration routine initialization within a
predetermined time period, performing stability analysis of the analyte
sensor, and time shifting the calibration routine initialization to start
at a time period different from the predetermined time period.

[0112]Time shifting may include executing the calibration routine
following the stability analyte of the sensor.

[0113]Time shifting may include delaying the calibration routine
initialization past the predetermined time period.

[0114]In one aspect, the analyte sensor may include a glucose sensor.

[0115]The determined stability profile may include a predetermined time
period during which the analyte sensor is stable.

[0118]In another embodiment, a method may include initializing an analyte
sensor, activating a timer associated with the analyte sensor, the timer
related to a stability profile of the analyte sensor, calibrating the
analyte sensor based on a time corresponding reference data based at
least in part on a predetermined calibration schedule, and modifying the
calibration schedule.

[0119]Initializing the analyte sensor may include determining sensor
stability.

[0120]The stability profile may include a predetermined time period
associated with the sensor stability.

[0121]The predetermined calibration schedule may include a plurality time
periods for performing calibration over the life of the sensor.

[0122]Modifying the calibration schedule may include time shifting the
plurality of time periods for performing calibration.

[0123]The reference data may be associated with a time corresponding
sensor data.

[0124]The reference data may be obtained from an in vitro blood glucose
meter.

[0125]In yet another embodiment, a method may include detecting an input
value associated with a reference data, verifying that an analyte sensor
is within its calibration stability duration, calibrating the analyte
sensor based on the detected input value, and time shifting one or more
subsequent scheduled calibration events for the analyte sensor.

[0126]The reference data may be received from a blood glucose monitor.

[0127]Calibrating the analyte sensor may include determining a sensitivity
value associated with the sensor.

[0128]The sensitivity may be determined based at least in part of the
detected input value associated with the reference data.

[0130]The sensor manufacturing information may include a date of
manufacture of the analyte sensor.

[0131]Various other modifications and alterations in the structure and
method of operation of this invention will be apparent to those skilled
in the art without departing from the scope and spirit of the invention.
Although the invention has been described in connection with specific
preferred embodiments, it should be understood that the invention as
claimed should not be unduly limited to such specific embodiments. It is
intended that the following claims define the scope of the present
invention and that structures and methods within the scope of these
claims and their equivalents be covered thereby.